title: Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch.
abstract: To elucidate the molecular mechanisms whereby expanded polyglutamine stretches elicit a gain of toxic function, we expressed full-length and truncated DRPLA (dentatorubral-pallidoluysian atrophy) cDNAs with or without expanded CAG repeats in COS-7 cells. We found that truncated DRPLA proteins containing an expanded polyglutamine stretch form filamentous peri- and intranuclear aggregates and undergo apoptosis. The apoptotic cell death was partially suppressed by the transglutaminase inhibitors cystamine and monodansyl cadaverine (but not putrescine), suggesting involvement of a transglutaminase reaction and providing a potential basis for the development of therapeutic measures for CAG-repeat expansion diseases.
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, Asahimachi Niigata, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Igarashi
authors.forename: R
authors.initials: R
authors.lastname: Koide
authors.forename: T
authors.initials: T
authors.lastname: Shimohata
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.forename: H
authors.initials: H
authors.lastname: Takano
authors.forename: H
authors.initials: H
authors.lastname: Date
authors.forename: M
authors.initials: M
authors.lastname: Oyake
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: A
authors.initials: A
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Egawa
authors.forename: T
authors.initials: T
authors.lastname: Ikeuchi
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: R
authors.initials: R
authors.lastname: Nakano
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: I
authors.initials: I
authors.lastname: Hozumi
authors.forename: T
authors.initials: T
authors.lastname: Inuzuka
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D019556:COS Cells; D002103:Cadaverine / Q000031:analogs & derivatives / Q000494:pharmacology; D003538:Cystamine / Q000494:pharmacology; D017931:DNA Primers; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000235:genetics; D011700:Putrescine / Q000494:pharmacology; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D011503:Transglutaminases / Q000037:antagonists & inhibitors*; D018911:Trinucleotide Repeats
chemical_list: D017931:DNA Primers; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; C095278:atrophin-1; D011503:Transglutaminases; C008542:monodansylcadaverine; D002103:Cadaverine; D003538:Cystamine; D011700:Putrescine